- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05926102
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS): A Pragmatic Trial of Precision Prostate Cancer Screening
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Prostate cancer is the most common non-cutaneous cancer in US men and in the Veterans Health Administration (VHA): 1 in 8 will be diagnosed with the disease in their lifetime. Many cases are non-lethal, but prostate cancer remains the 2nd leading cause of cancer death among US men, representing 2.5% of all deaths. VHA diagnoses >16,000 new cases annually and cares for >400,000 men living with prostate cancer. As a result, prostate cancer diagnosis and treatment is a national priority for VHA.
A major impediment to reducing the incidence of metastatic prostate cancer and prostate cancer death is the lack of an optimal screening strategy to identify men at high risk. Screening with prostate-specific antigen (PSA) testing modestly reduces prostate cancer deaths but at the cost of overdiagnoses and overtreatment. Current screening approaches do not adequately distinguish men without prostate cancer or with low-grade prostate cancer amenable to active surveillance from men with clinically significant prostate cancer, who need treatment. As a result, clinical guidelines do not recommend universal prostate cancer screening, including those from the United States Preventive Services Task Force (USPSTF) and the VHA National Center for Health Promotion and Disease Prevention. Still, many men undergo screening based on variable and subjective assessments of their race/ethnicity, family history, and other risk factors.
A new paradigm of precision screening could improve the benefit-to-harm ratio of screening by implementing screening strategies tailored to an individual's specific genetic profile. Due to advances in high-throughput genotyping and sequencing, increasingly large and diverse cohort studies, and standardization of genetic variant classification, germline genetic testing is emerging as a powerful predictor for prostate cancer, including metastatic and lethal disease. This includes both rare highly penetrant variants and polygenic risk scores (PRS), which characterize an individual's predisposition to prostate cancer due to common genetic variation. Rare and common genetic variation is now an equally powerful predictor of clinically significant disease as self-reported race or family history, including in the Million Veteran Program.
This clinical trial will evaluate the promise of precision risk stratification to identify men most likely to benefit from prostate cancer screening. During the proof-of-concept phase, the investigators will achieve the following aims:
- Develop a precision prostate cancer screening intervention consisting of genetic testing for rare variants and a transancestry PRS, delivered to participants and their primary care providers along with individualized, genetic risk-informed screening recommendations.
- Determine the feasibility of enrolling men aged 55-70 ( 35% of whom are of racial/ethnic minority groups) to a pragmatic randomized clinical trial (RCT) comparing the precision screening intervention to usual care.
- Perform an interim assessment to determine whether the observed trajectory of negative prostate biopsy event rates is consistent with rates needed to detect a meaningful between-group difference at the end of the 7-year project period.
If the investigators demonstrate feasibility of enrollment and adequate event rates during the proof-of-concept phase, the RCT will continue to the clinical trial phase to test the following co-primary hypotheses:
Compared with men in the usual care arm, men in the precision screening arm will have a time-to-diagnosis of clinically significant prostate cancer (csPCa, defined as NCCN classification intermediate risk or higher) that is not inferior by a margin of >30 days over a median 4 years of follow-up.
a. If non-inferiority is demonstrated, the investigators will sequentially test the hypothesis that time-to-diagnosis of csPCa is shorter in the precision screening arm than in the usual care arm (superiority).
- Compared with usual care, men in the precision screening arm overall will undergo fewer negative prostate biopsies over a median 4 years of follow-up.
Pre-specified subgroup analyses will test these hypotheses in Black men specifically, to evaluate whether this population benefits equally or more from the intervention. Enrollees will be followed for additional outcomes including all prostate cancer diagnoses, PSA testing, prostate MRI, rare variants identified, preferences for or against prostate cancer screening, and health-related quality of life.
The investigators expect that precision screening will increase screening among high-risk patients but decrease screening among low- and average-risk patients, thereby maintaining or improving overall csPCa detection while improving the population-level benefit-to-harm ratio. Rigorous RCT evidence that genetic risk-informed screening maintains the benefits of screening while minimizing the harms of unnecessary procedures and treatments among low-risk men will change clinical practice and policy around prostate cancer screening.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Charles A Brunette, PhD
- Phone Number: (857) 364-6324
- Email: charles.brunette@va.gov
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02130-4817
- Recruiting
- VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
-
Contact:
- Charles A Brunette, PhD
- Phone Number: 857-364-6324
- Email: charles.brunette@va.gov
-
Principal Investigator:
- Jason L Vassy, MD MPH
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- baseline age 55-69 years
- receipt of regular VA care
- Veteran status
Exclusion Criteria:
- personal history of prostate cancer
- prior prostate biopsy, prostatectomy, or prostate MRI
- known carrier status of rare variant associated with cancer syndrome
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Screening
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Precision screening intervention
The precision screening intervention will consist of an interpreted prostate cancer genetic risk assessment (GRA) report, provided to the participant along with tailored prostate cancer screening recommendations and, in cases of high genetic risk, genetic counseling.
The risk report and supporting educational materials will also be provided to the participant's primary care provider.
Usual care in this study includes receipt of a brief brochure about shared decision-making in prostate cancer screening.
|
The precision screening intervention will consist of an interpreted prostate cancer genetic risk assessment (GRA) report, provided to the participant along with tailored prostate cancer screening recommendations and, in cases of high genetic risk, genetic counseling.
The risk report and supporting educational materials will also be provided to the participant's primary care provider.
Usual care in this study includes receipt of a brief brochure about shared decision-making in prostate cancer screening.
Usual care in this study includes receipt of a brief brochure about shared decision-making in prostate cancer screening.
|
Experimental: Usual care
Usual care in this study includes receipt of a brief brochure about shared decision-making in prostate cancer screening.
|
Usual care in this study includes receipt of a brief brochure about shared decision-making in prostate cancer screening.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Diagnosis of clinically significant prostate cancer
Time Frame: 7 years
|
Cases of csPCa will be abstracted from VA and survey data and defined using NCCN classifications of intermediate risk or higher: PSA 10 and/or Grade Group 2 and/or clinical T stage T2b
|
7 years
|
Negative prostate biopsy
Time Frame: 7 years
|
Counts of negative prostate biopsies not temporally associated with csPCa (within 6 months of diagnosis) will be abstracted from VA and survey data
|
7 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Diagnosis of prostate cancer
Time Frame: 7 years
|
All cases of prostate cancer will be abstracted from VA and survey data
|
7 years
|
PSA testing
Time Frame: 7 years
|
PSA testing will be identified from VA and survey data
|
7 years
|
Prostate MRI
Time Frame: 7 years
|
Prostate magnetic resonance imaging will be identified from VA and survey data
|
7 years
|
Self-rated health
Time Frame: 7 years
|
Self-rated health will be collected at the baseline survey and every 6 months with a single-item self-rating of health on a Likert scale from "poor" to "excellent.
|
7 years
|
Quality of life
Time Frame: 5 years
|
Health-related quality of life is collected through the Veterans RAND 12-Item Health Survey (VR-12) on the baseline survey and at each participant's 5-year survey or last survey
|
5 years
|
Prostate biopsy
Time Frame: 7 years
|
Counts of all prostate biopsies will be abstracted from VA and survey data.
|
7 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adherence to precision cancer screening recommendations
Time Frame: 7 years
|
The precision screening intervention will include the recommendation that high-risk men undergo PSA screening and that low-risk men not undergo screening.
The investigators will define adherence to the intervention in these two groups of men as the presence and absence of PSA testing, respectively, during the observation period.
|
7 years
|
Acceptability of the precision prostate cancer screening intervention
Time Frame: 7 years
|
The survey will assess patient acceptability of the precision screening with a 3-item instrument assessing patient perspective on the 1) amount of information presented, 2) length of the information, 3) clarity of the information, with each domain scored on a 5-point Likert scale.
|
7 years
|
Rare pathogenic/likely pathogenic variants
Time Frame: 7 years
|
Proportion of participants with a rare P/LP variant associated with hereditary prostate cancer
|
7 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Jason L Vassy, MD MPH, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ONCA-021-22F
- I01CX002635 (Other Grant/Funding Number: VA CSR&D)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ANALYTIC_CODE
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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